You Jian, Cui Fu-de, Han Xu, Wang Yong-sheng, Yang Lei, Yu Ying-wei, Li Qing-po
Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, No.103, Wenhua Road, Shenyang 110016, China.
Colloids Surf B Biointerfaces. 2006 Mar 1;48(1):35-41. doi: 10.1016/j.colsurfb.2005.12.011. Epub 2006 Feb 9.
The purpose of this study was to design a sustained-release formulation of an oily drug. The sustained-release microspheres with self-emulsifying capability containing zedoary turmeric oil (ZTO) were prepared by the quasi-emulsion-solvent-diffusion method. The micromeritic properties, the efficiency of emulsification and the drug-release behavior of the resultant microspheres were investigated. The bioavailability of the microspheres was compared with conventional ZTO self-emulsifying formulations for oral administration using 12 healthy rabbits. An HPLC method was employed to determine the concentration of germacrone in plasma, which was used as an index of ZTO. Spherical and compacted microspheres with average diameters of 100-600 microm have been prepared, and their release behavior in distilled water containing 1.2% (w/v) of polysorbate-80 can be controlled by the ratio of polymer/Areosil200 in the microspheres. The resultant emulsions with mean droplet sizes of 200-500 nm are produced when the microspheres are immersed in phosphate buffer (pH 6.8) under gentle agitation. The stability and the droplet size of the resultant emulsions are also affected by the polymer/Areosil200 ratio in the formulation, while the amount of talc has a marked effect on the self-emulsifying rate. The plasma concentration-time profiles with improved sustained-release characteristics were achieved after oral administration of the microspheres with a bioavailability of 135.6% with respect to the conventional self-emulsifying formulation (a good strategy for improving the bioavailability of an oily drug). In conclusion, the sustained-release microspheres with self-emulsifying capability containing ZTO have an improved oral bioavailability. Our study offers an alternative method for designing sustained-release preparations of oily drugs.
本研究的目的是设计一种油性药物的缓释制剂。采用准乳液-溶剂扩散法制备了含莪术油（ZTO）的具有自乳化能力的缓释微球。考察了所得微球的粉体学性质、乳化效率和药物释放行为。将微球的生物利用度与12只健康家兔口服的传统ZTO自乳化制剂进行比较。采用高效液相色谱法测定血浆中莪术酮的浓度，以其作为ZTO的指标。制备了平均直径为100 - 600微米的球形且紧密的微球，其在含1.2%（w/v）聚山梨酯80的蒸馏水中的释放行为可通过微球中聚合物/气相二氧化硅200的比例来控制。当微球在温和搅拌下浸入磷酸盐缓冲液（pH 6.8）中时，可产生平均粒径为200 - 500纳米的乳液。所得乳液的稳定性和液滴大小也受制剂中聚合物/气相二氧化硅200比例的影响，而滑石粉的用量对自乳化速率有显著影响。口服微球后获得了具有改善的缓释特性的血浆浓度-时间曲线，相对于传统自乳化制剂，生物利用度为135.6%（这是提高油性药物生物利用度的一种良好策略）。总之，含ZTO的具有自乳化能力的缓释微球具有提高的口服生物利用度。我们的研究为设计油性药物的缓释制剂提供了一种替代方法。
